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Once-daily oral ritlecitinib or brepocitinib versus placebo in patients with moderate-to-severely active Crohn's disease (PIZZICATO): an international, randomised, phase 2a trial - PubMed

7 hours ago
  • #JAK inhibitors
  • #Crohn's disease
  • #clinical trial
  • The PIZZICATO trial evaluated once-daily oral ritlecitinib (a JAK3/TEC inhibitor) and brepocitinib (a TYK2/JAK1 inhibitor) versus placebo in patients with moderate-to-severely active Crohn's disease (CD).
  • This was an international, randomized, phase 2a study with a 12-week induction phase followed by a 52-week open-label extension (OLE) phase.
  • Patients (18-75 years old) with confirmed CD and prior treatment failure were randomized to ritlecitinib (200 mg then 50 mg), brepocitinib (60 mg), or placebo.
  • Primary efficacy endpoint: ≥50% reduction in Simple Endoscopic Score for CD (SES-CD 50) at Week 12. Both drugs showed significant improvement over placebo (ritlecitinib: 14.3%, p=0.012; brepocitinib: 21.4%, p=0.0012).
  • Safety profiles were acceptable, with most treatment-emergent adverse events (TEAEs) being mild or moderate. Common TEAEs included SARS-CoV-2 infection and worsening CD.
  • The study suggests preliminary efficacy for ritlecitinib and brepocitinib in moderate-to-severe CD, but further research is needed for milder cases and responder populations.
  • Funding and conflicts: Pfizer Inc. funded the study; multiple authors disclosed ties to pharmaceutical companies, including Pfizer, AbbVie, and Janssen.